Rongjing He, Yongheng Zhang, Shushu Ding, Anwei Zhu, Guoyue Shi
Implantable bioelectronic interfaces are central to decoding neurochemical dynamics, yet in vivo deep-tissue monitoring is often limited by three obstacles: insertion trauma from bulky substrates, the mechanical fragility of conventional nanopipette microsensors, and nonspecific interference in the complex neural microenvironment. Herein, we present a density functional theory (DFT)-assisted dual-recognition design strategy implemented in an acupuncture needle-based extended-gate field-effect transistor (AN-EGFET) neuroprobe to address these bottlenecks through a customized dual-recognition material architecture. Built on a mechanically robust yet ultrafine acupuncture needle, the device integrates a sensing interface composed of gold nanoparticles, a poly(o-phenylenediamine) molecularly imprinted polymer (MIP), and 4-mercaptophenylboronic acid (4-MPBA). The imprinted cavities provide shape and size complementarity, while the boronate group binds the catechol moiety of dopamine (DA); acting together, these two recognition modes enhance selective DA capture and stable signal transduction under biologically relevant conditions, yielding detection and quantification limits of 1.66 nM and 5.43 nM, respectively. Molecular dynamics (MD) simulations indicate that cooperative noncovalent interactions within the cavity promote the pre-concentration and retention of DA, thereby facilitating subsequent 4-MPBA boronate-affinity anchoring. Beyond real-time tracking of DA release in vitro, we evaluate the in vivo monitoring capability of the AN-EGFET including regional discrimination of DA signals, monitoring of pharmacologically modulated DA responses, and differentiation of striatal DA levels between healthy and Parkinson's disease model mice. The AN-EGFET provides a low-damage and robust implantable bioelectronic interface for real-time DA monitoring in vivo, with potential utility in basic neuroscience research and preclinical studies of Parkinson's disease-related neurochemical changes.